Diagnosis of canine lymphoid neoplasia using clonal rearrangements of antigen receptor genes

Diagnosis of canine lymphoid neoplasia using clonal rearrangements of antigen receptor genes
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DOI:
10.1354/vp.40-1-32
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发表时间:
2003-01-01
影响因子:
2.4
通讯作者:
Avery, AC
Avery, AC
中科院分区:
农林科学2区
文献类型:
--
作者:
Burnett, RC;Vernau, W;Avery, AC

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虽然犬白血病和淋巴瘤的晚期诊断通常并不复杂,但一些疾病的表现可能是诊断的挑战。在某些情况下,淋巴瘤和白血病很难与淋巴细胞的良性反应性增殖区分开来。由于克隆性是恶性肿瘤的标志,我们开发了一种检测方法,使用聚合酶链反应来扩增免疫球蛋白基因和t细胞受体基因的可变区域,以检测克隆淋巴细胞群的存在。该试验在77只淋巴细胞恶性肿瘤犬中检测到91%的克隆重排抗原受体基因。在接受测试的24只狗中,无论是健康的还是患有与淋巴细胞恶性肿瘤无关的明确疾病的狗,在一只(感染了犬埃利希体的狗)身上发现了克隆重排的抗原受体基因。基因重排符合免疫表型(免疫球蛋白基因重排适用于b细胞白血病,t细胞受体基因重排适用于t细胞白血病)。稀释分析显示,当0.1-10%的DNA来自肿瘤细胞时,根据来源组织的不同,可以检测到克隆重排。该检测的潜在应用包括诊断活检样本、腔液、细针抽吸液、骨髓和外周血中的淋巴瘤或白血病;谱系(B细胞或T细胞)的测定;淋巴瘤分期;以及化疗后残留病变的检测。
Although the diagnosis of canine leukemia and lymphoma in advanced stages is usually uncomplicated, some presentations of the disease can be a diagnostic challenge. In certain situations, lymphoma and leukemia can be difficult to distinguish from a benign reactive proliferation of lymphocytes. Because clonality is the hallmark of malignancy, we have developed an assay that uses the polymerase chain reaction to amplify the variable regions of immunoglobulin genes and T-cell receptor genes to detect the presence of a clonal lymphocyte population. The assay detected clonally rearranged antigen receptor genes in 91% of the 77 dogs with lymphoid malignancy. Of the 24 dogs tested, that were either healthy or had clearly defined conditions not related to lymphoid malignancy, a clonally rearranged antigen receptor gene was found in one (a dog with Ehrlichia canis infection). Gene rearrangement was appropriate for the immunophenotype (immunoglobulin gene rearrangement in B-cell leukemias and T-cell receptor gene rearrangement in T-cell leukemias). Dilution analysis showed that the clonal rearrangement could be detected when 0.1-10% of the DNA was derived from neoplastic cells, depending on the source tissue. Potential applications of this assay include the diagnosis of lymphoma or leukemia in biopsy samples, cavity fluids, fine needle aspirates, bone marrow and peripheral blood; the determination of lineage (B or T cell); staging of lymphoma; and detection of residual disease after chemotherapy.